The overall objective of the proposed research is to establish the suitability of woodchuck hepatitis as an animal model for the study of hepatitis B and liver cancer in man. The woodchuck hepatitis virus (WHV) is almost identical in morphology to hepatitis B virus (HBV), the agent of human hepatitis. It contains a DNA-dependent DNA polymerase and a substantial single-stranded region in each DNA molecule. Electron micrographs of woodchuck serum have demonstrated three characteristic particles, one resembling the well-known Dane particle and the others the tubular and spherical forms of outer coat protein (HBsAg) so common in the sera of patients with hepatitis B. The proposed research plan involves five areas of investigation: (1) characterization of the virus (WHV), (2) potential infectivity of HBV to woodchucks (Marmota monax), (3) epidemiology of WHV in natural populations of woodchucks, (4) pathology of woodchucks hepatitis and primary hepatocellular carcinoma (PHC), and (5) study of significant biological traits of the experimental animal. The woodchuck colony in the Penrose Research Laboratory has an unusually high frequency of occurrence of PHC, 35 cases in 139 necropsies completed. The discovery of integrated WHV-DNA in DNA derived from woodchuck liver tumors is reason for a more intensive study of the replicative cycle of this virus and its potential for causing liver cancers.